5-Aminosalicylic acid (5-ASA) is mainly used in industries of medicines, pesticides, etc. Methods for synthesizing 5-ASA currently reported in literatures mainly include four types of process routes: aniline process, salicylic acid method, p-aminophenol carboxylated and p-acetaminophenol carboxylated solid phase synthesis method. They are respectively outlined as follows:
1. Synthetic Process from Aniline
In the patent JP 6340600 disclosed in Japan, the aniline process uses aniline as a starting material to obtain an aniline diazonium salt, which is then coupled with salicylic acid, and then the azo bond is cleaved by reduction to obtain one molecule of 5-ASA while removing another molecule of aniline (see reaction (1) below). Moreover, in another literature (Zhu Zhi-qing et al., Preparation of mesalamine by catalytic hydrogenolysis, Chinese Journal of Pharmaceuticals, 1999, 30(1):8˜9), the azo bond is reduced by hydrogen gas using Raney-Ni as catalyst, to obtain 5-ASA (see reaction (2) below), and the yield of this route reported by the literature is no more than 50%. Although the method is easy to operate, it is not suitable for the production because the process route is long, and aniline and azo compounds are toxic, and are environmentally hazardous to some extent, and are easily introduced into the final product by raw materials, thus seriously affect the purity of the product and thereby resulting in increased costs for the purification.
The synthetic route of this process is as follows:

2. Synthetic Process from Salicylic Acid
The salicylic acid process is disclosed in China Patent Application Publication No.: CN 1053229A and the literature (Yan Ting-ren et al., Improved Preparation of Mesalamine, Chinese Journal of Pharmaceuticals, 1994, 25(14):539˜540), in which salicylic acid is used as a starting material and is nitrified by conc. nitric acid to obtain 5-nitrosalicylic acid, and then the nitro group is reduced to an amino group under an acidic condition using iron powder as reducing agent (a preferred condition is hydrochloric acid and iron powder), and 5-ASA is precipitated in a weak acidic condition after treatments (see reaction 3). The total yield of this route is about 50%, and the advantages of this route are that the raw materials are easily available, and the route is simple, so that this route has certain practical values. The disadvantages are that the method suffers from the considerable amount isomers impurity formed by the nitration, which resulted in difficulties for the purification of the product and low yield. Meanwhile, the nitro compounds produced during the Intermediate process are introduced into the final product, so that it is difficult for the amount of nitro compound impurity in 5-ASA product to achieve the requirements for medical applications. In addition, serious environmental pollution will also be caused due to the great amount of nitric acid and iron powder employed in the reactions.
The synthetic route of this process is as follows:

3. p-Aminophenol Carbon Dioxide Carboxylated Solid Phase Synthesis Method
It is reported by MO Fen Zhu, et al. in “A New Method for Synthesis of Mesalamine that p-aminophenol”, Chinese Journal of Pharmaceuticals (1997, 28(8):341˜342) that 5-ASA is prepared by reacting p-aminophenol as a starting material with carbon dioxide in a gas phase condition under high pressure and high temperature. This literature simply reports the preparation of 5-ASA by this process and the total yield is over 80%. This process is short in process route, less pollution, and harsh in reaction conditions. However, since the gas-solid carboxylation is performed under high pressure and high temperature, aminophenol is easily oxidized and polymerized. In a addition to the above literature, no any further related patent applications or papers have been published.
The synthetic route of the process of carboxylation of p-aminophenol is as follows:

Conventional synthetic process from aniline or salicylic acid method are still employed in the majority of production processes for 5-aminosalicylic acid, both at home and abroad.
4. Process of Solid Phase Carboxylation of p-Acetaminophenol
It is disclosed in Indian patent IN 2004MU01242 by Kumar et al. that 5-ASA is prepared by performing carboxylation reaction in the presence of a solid base and CO2 under high pressure and high temperature, using p-acetaminophenol as a starting material, but the yield is not reported in this patent. This method has the advantage of simple process and shows certain prospects for industrial applications, but the method reported by this patent is carried out in a condition without a catalyst, thus the reaction rate is slow and the reaction time is as long as 12˜24 h. Also, the energy consumption is high and the gas-solid reaction has a poor contact, and is easily overheated locally, causing side reactions such as oxidation and polymerization, resulting in high amount of impurities in the crude product, which is difficult for the purification. So far, no research reports and application examples associated with this process have been found yet.
The synthetic route of this process is as follows:
